This information about the management of rash and dermatologic effects during anti-EGFR treatment is not intended to recommend any particular anti-EGFR treatment or treatment related to rash or dermatologic effects. Any treatment decisions are the sole responsibility of the healthcare professional.
Inhibition of the human epidermal growth factor receptor (EGFR) by targeted agents is one of the most widely studied approaches to cancer treatment. Generally speaking, while these agents avoid many of the side effects associated with traditional chemotherapeutic agents, they are not without side effects.
EGFR is found on many tumor types as well as on normal skin cells. Therefore, blocking EGFR can lead to various dermatologic effects, including rash, skin dryness, and nail changes.1
It is recommended that patients wear sunscreen and hats and limit sun exposure while receiving Vectibix® since sunlight can exacerbate any skin reactions that may occur.
Representative dermatologic toxicities in patients receiving Vectibix® in clinical studies
Dermatitis acneiform
EGFR Rash
Paronychia
Rash related to anti-EGFR therapy typically appears within the first 2 weeks of treatment:
• Most cases are mild or moderate (grade 1 or 2).1,2 However, complications can occur. Please see boxed warning.For rash associated with Vectibix®:
• Early intervention is important.1,4
– Start treatment at the first sign of rash
– Look for the presence of pain, cracked skin, or drainage from the rash
• It may be helpful in some cases to treat papules or pustules with topical antiseptic or antibiotic to mitigate lesion severity and prevent infection.1,4-6
– Limit use of gel formulations to isolated/scattered papules and pustules so as not to exacerbate dry skin; lotions and creams are typically preferred, especially for widespread lesions
– In moderate to severe cases, use of oral antibiotics has been shown to be effective in preventing secondary bacterial infections4,5
• Mild, localized itching may benefit from a topical antihistamine; oral antihistamines can help relieve severe itching.1,4
• The role of steroids is unclear at present. However, currently the use of topical corticosteroids is not recommended.1,4,6
• Keep in mind that the use of over-the-counter acne preparations is generally not recommended due to exacerbation of dryness and peeling.2,5,7,8
• Liquid bandages can be used in cases of fissuring.1,4,6
• Patients who experience dermatologic effects should be monitored for inflammatory or infectious sequelae, with appropriate treatment promptly initiated.5,6
• Consider pain relief intervention as needed.2
• Consider a dermatology consult in severe or unusual patient cases.
For nail changes:
• Symptomatic relief may be achieved with the use of antiseptic soaks and by cushioning the affected area(s).1
• Topical corticosteroids can reduce redness and treat severe lesions.5
• Liquid bandages to cover fissuring can be beneficial.1
• Topical colloidal silver products may be used for bleeding.7
• Silver nitrate may be helpful for pyogenic (pus-producing) granuloma-like lesions with excessive granulation tissue.5
• Bacterial superinfections should be treated with oral antibiotics.5
References
1. Sipples R. Common side effects of anti-EGFR therapy: acneform rash. Semin Oncol Nurs. 2006;22:28-34.
2. Pérez-Soler R, Delord JP, Halpern A, et al. HER1/EGFR inhibitor associated rash: future directions for management and investigation outcomes from the HER1/EGFR Inhibitor Rash Management Forum. Oncologist. 2005;10:345-356.
3. Krozely P. Epidermal growth factor receptor tyrosine kinase inhibitors: evolving role in the treatment of solid tumors. Clin J Oncol Nurs. 2004;8:163-168.
4. Rhee J, Oishi K, Garey J, Kim E. Management of rash and other toxicities in patients treated with epidermal growth factor receptor–targeted agents. Clin Colorectal Cancer. 2005;5:S101-S106.
5. Dick SE, Crawford GH. Managing cutaneous side effects of epidermal growth factor receptor (HER1/EGFR) inhibitors. Commun Oncol. 2005;2:492-496.
6. Garey JS, Oishi KJ, Burke B, Kim ES. Treatment of skin rash in a phase II study of cisplatin, docetaxel, and erlotinib in patients with advanced head and neck cancer: a prospective algorithmic approach. J Clin Oncol. 2005;23:786s. Abstract 8231.
7. Segaert S, Van Cutsem E. Clinical signs, pathophysiology and management of skin toxicity during therapy with epidermal growth factor receptor inhibitors. Ann Oncol. 2005;16:1425-1433.
8. Pizzo B. New directions in oncology nursing care: focus on gefitinib in patients with lung cancer. Clin J Oncol Nurs. 2004;8:385-392.
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Vectibix® is indicated as a single agent for the treatment of EGFR-expressing, metastatic colorectal carcinoma (mCRC) with disease progression on or following fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens.
The effectiveness of Vectibix® as a single agent for the treatment of EGFR-expressing mCRC is based on progression-free survival. Currently no data are available that demonstrate an improvement in disease related symptoms or increased survival with Vectibix®.
Important Safety Information
Safety data are available from 15 clinical trials in which 1,467 patients received Vectibix®; of these, 1,293 received Vectibix® monotherapy and 174 received Vectibix® in combination with chemotherapy.
WARNING Infusion Reactions: Severe infusion reactions occurred with the administration of Vectibix® in approximately 1% of patients. Severe infusion reactions were identified by reports of anaphylactic reaction, bronchospasm, fever, chills, and hypotension. Although fatal infusion reactions have not been reported with Vectibix®, fatalities have occurred with other monoclonal antibody products. Stop infusion if a severe infusion reaction occurs. Depending on the severity and/or persistence of the reaction, permanently discontinue Vectibix®.
Dermatologic Toxicity:Dermatologic toxicities, related to Vectibix® blockade of EGF binding and subsequent inhibition of EGFR-mediated signaling pathways, were reported in 89% of patients and were severe (NCI-CTC grade 3 and higher) in 12% of patients receiving Vectibix® monotherapy. The clinical manifestations included, but were not limited to, dermatitis acneiform, pruritus, erythema, rash, skin exfoliation, paronychia, dry skin, and skin fissures. Severe dermatologic toxicities were complicated by infection including sepsis, septic death, and abscesses requiring incisions and drainage. Withhold or discontinue Vectibix® and monitor for inflammatory or infectious sequelae in patients with severe dermatologic toxicities.
Vectibix® is not indicated for use in combination with chemotherapy with or without bevacizumab. In an interim analysis of a randomized (1:1) clinical trial of patients with previously untreated metastatic colorectal cancer, the addition of Vectibix® to the combination of bevacizumab and chemotherapy resulted in decreased progression-free survival (n=947) and increased incidence of NCI-CTC grade 3-5 (87% vs. 72%) adverse reactions (n=926).
In a single-arm study of 19 patients receiving Vectibix® in combination with IFL, the incidence of NCI-CTC grade 3-4 diarrhea was 58%; in addition, grade 5 diarrhea occurred in 1 patient. In a single-arm study of 24 patients receiving Vectibix® plus FOLFIRI, the incidence of NCI-CTC grade 3 diarrhea was 25%.
Pulmonary fibrosis occurred in less than 1% (2/1,467) of patients in clinical trials of Vectibix®. Following the initial fatality, patients with a history of interstitial pneumonitis, pulmonary fibrosis, and evidence of interstitial pneumonitis were excluded from clinical studies. Therefore, the estimated risk in such patients is uncertain. Permanently discontinue Vectibix® therapy in patients developing interstitial lung disease, pneumonitis, or lung infiltrates.
In the randomized, controlled clinical trial, median magnesium levels decreased by 0.1 mmol/L in the Vectibix® arm. Additionally, hypomagnesemia (NCI-CTC grade 3 or 4) requiring electrolyte repletion occurred in 2% of patients 6 weeks or longer after the initiation of Vectibix®. In some patients, hypomagnesemia was associated with hypocalcemia. Patients should be periodically monitored, and treated appropriately, for hypomagnesemia and hypocalcemia during and for 8 weeks after the completion of Vectibix® therapy.
It is recommended that patients wear sunscreen and hats and limit sun exposure while receiving Vectibix®, since sunlight can exacerbate any skin reactions that may occur.
In women of childbearing potential, appropriate contraceptive measures must be used during, and for 6 months after, treatment with Vectibix®.
The most common adverse events observed in clinical studies of Vectibix® (n = 1,467) were skin rash with variable presentations, hypomagnesemia, paronychia, fatigue, abdominal pain, nausea, and diarrhea, including diarrhea resulting in dehydration. The most serious adverse events observed were pulmonary fibrosis, severe dermatologic toxicity complicated by infectious sequelae and septic death, infusion reactions, abdominal pain, hypomagnesemia, nausea, vomiting, and constipation.
